Synthesis and characterization of a PAMAM dendrimer nanocarrier functionalized by LDP14 peptide for targeted drug delivery to the brain thesis submitted for MsC degree in Medical Nanotechnology Researcher

Abstract

Introduction: Today, one of the concerns of pharmaceutical scientists is the synthesis of suitable carriers for brain drug delivery, which has advantages such as good compatibility, high biodegradability, and capability of transport through the blood-brain barrier. In this study, we aimed to synthesize new dendrimer-based nanoparticles for targeted gene delivery to glioma, which can cross the blood-brain barrier with high specificity and cause the least damage to the central nervous system.

Methods: In this study, The LDP14 peptide was linked on G4 PAMAM dendrimers using bifunctional PEG, and the physicochemical properties of nanoparticles were determined by FTIR, NMR, DLS, and TEM. Finally, cellular uptake of these nanoparticles and the efficiency of PEGFP-N1 transfection by C6 glioma cells were studied by fluorescent microscopy and flow cytometry.

Results: In vitro studies showed that LDP14-modified nanoparticles have good transfection efficacy and proper uptake by c6 glioma cell line. Results also showed that LDP14 is a ObRs ligand and LDP14-modified nanoparticles internalized by receptor-mediated endocytosis to C6 glioma cells.

Conclusion: Our result showed that, LDP14-modified nanoparticles provide a safe and effective nanocarrier for brain gene delivery.